Is it best to expect the worst? Influence of patients' side-effect expectations on endocrine treatment outcome in a 2-year prospective clinical cohort study.

BACKGROUND: This study aims to determine the role of patient expectations as potentially modifiable factor of side-effects, quality of life, and adherence to endocrine treatment of breast cancer. PATIENTS AND METHODS: A 2-year prospective clinical cohort study was conducted in routine primary care with postoperative patients with hormone-receptor-positive breast cancer, scheduled to start adjuvant endocrine treatment. Structured patient-reported assessments of side-effects, side-effect expectations, quality of life, and adherence took place during the first week post-surgery and after 3 and 24 months of endocrine treatment. RESULTS: Of 111 enrolled patients, at 3 and 24 months, 107 and 88 patients, respectively, were assessed. After 2 years of endocrine treatment, patients reported high rates of side-effects (arthralgia: 71.3%, weight gain: 53.4%, hot flashes: 46.5%), including symptoms not directly attributable to the medication (breathing problems: 28.1%, dizziness: 25.6%). Pre-treatment expectations significantly predicted patient-reported long-term side-effects and quality of life in multivariate models controlling for relevant medical and psychological variables. Relative risk of side-effects after 2 years of endocrine treatment was higher in patients with high negative expectations at baseline than in those with low negative expectations (RR = 1.833, CI 95%, 1.032-3.256). A significant interaction confirmed this expectation effect to be particularly evident in patients with high side-effects at 3 months. Furthermore, baseline expectations were associated with adherence at 24 months (r = -0.25, P = 0.006). CONCLUSIONS: Expectations are a genuine factor of clinical outcome from endocrine treatment for breast cancer. Negative expectations increase the risk of treatment-specific side-effects, nocebo side-effects, and non-adherence. Yet, controlled studies are needed to analyze potential causal relationships. Optimizing individual expectations might be a promising strategy to improve side-effect burden, quality of life, and adherence during longer-term drug intake. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02088710.

Rethinking psychopharmacotherapy: The role of treatment context and brain plasticity in antidepressant and antipsychotic interventions.

Emerging evidence indicates that treatment context profoundly affects psychopharmacological interventions. We review the evidence for the interaction between drug application and the context in which the drug is given both in human and animal research. We found evidence for this interaction in the placebo response in clinical trials, in our evolving knowledge of pharmacological and environmental effects on neural plasticity, and in animal studies analyzing environmental influences on psychotropic drug effects. Experimental placebo research has revealed neurobiological trajectories of mechanisms such as patients' treatment expectations and prior treatment experiences. Animal research confirmed that "enriched environments" support positive drug effects, while unfavorable environments (low sensory stimulation, low rates of social contacts) can even reverse the intended treatment outcome. Finally we provide recommendations for context conditions under which psychotropic drugs should be applied. Drug action should be steered by positive expectations, physical activity, and helpful social and physical environmental stimulation. Future drug trials should focus on fully controlling and optimizing such drug×environment interactions to improve trial sensitivity and treatment outcome.

Is somatosensory amplification a risk factor for an increased report of side effects? Reference data from the German general population.

OBJECTIVE: The study investigates the association between somatosensory amplification and the reporting of side effects. It establishes a German version of the Somatosensory Amplification Scale and examines its psychometric properties in a representative sample of the German population. METHODS: Sample size was 2.469, with 51% taking any medication. Participants answered the Somatosensory Amplification Scale, Generic Assessment of Side Effects Scale, and indicated whether they were taking any medication and the type of medication. Correlational analysis and binary logistic regression were performed. RESULTS: When examining a subsample reporting both medication intake and general bodily symptoms, participants higher in somatosensory amplification rated more of their general bodily symptoms as medication-attributed side effects. However, somatosensory amplification scores were not associated with the intake of any type of medication. In the overall sample, higher somatosensory amplification scores were associated with an increased report of bodily symptoms. Additionally, participants with higher somatosensory amplification reported intake of a greater number of different medications. The psychometric properties of the translated scale were good, and previously established associations of somatosensory amplification with demographic variables (age, sex) were replicated. CONCLUSION: Results suggest a possible attributional bias concomitant to somatosensory amplification which in turn may increase the reporting of side effects after medication intake.

Health psychology and distress after haematopoietic stem cell transplantation.

The purpose of this study of 23 adult haematopoietic stem cell transplantation (HSCT) recipients is to compare the presence of post-transplantation depression disorders by gender and to compare the outcomes among those with and without depressive disorders using a health psychology focus. This cross-sectional pilot study of mid-term survivors took place in hospital outpatient clinic. Main outcome measures are depression disorders, health status (Short Form-12) and health anxiety. Female survivors had a higher rate of depression disorders, but those with treated depressive disorders were similar to those without depression on health-related quality of life and health anxiety. Neither patient age nor time since HSCT was associated with depressive disorders. A health psychology approach may enhance management of HSCT survivorship.

Resource utilization of patients with hypochondriacal health anxiety and somatization.

OBJECTIVES: To examine the resource utilization of patients with high levels of somatization and health-related anxiety. DESIGN: Consecutive patients on randomly chosen days completed a self-report questionnaire assessing somatization and health-related, hypochondriacal anxiety. Their medical care utilization in the year preceding and following completion of the questionnaire was obtained from an automated patient record. The utilization of patients above and below a predetermined threshold on the questionnaire was then compared. PATIENTS AND SETTING: Eight hundred seventy-six patients attending a primary care clinic in a large, urban, teaching hospital. OUTCOME MEASURES: Number of ambulatory physician visits (primary care and specialist), outpatient costs (total, physician services, and laboratory procedures), proportion of patients hospitalized, and proportion of patients receiving emergency care. RESULTS: Patients in the uppermost 14% of the clinic population on somatization and hypochondriacal health anxiety had appreciably and significantly higher utilization in the year preceding and the year following completion of the somatization questionnaire than did the rest of the patients in the clinic. After adjusting for group differences in sociodemographic characteristics and medical comorbidity, significant differences in utilization remained. In the year preceding the assessment of somatization, their adjusted total outpatient costs were $1,312 (95% CI $1154, $1481) versus $954 (95% CI $868, $1057) for the remainder of the patients and the total number of physician visits was 9.21 (95% CI 7.94, 10.40) versus 6.33 (95% CI 5.87, 6.90). In the year following the assessment of somatization, those above the threshold had adjusted total outpatient costs of $1,395 (95% CI $1243, $1586) versus $1,145 (95% CI $1038, $1282), 9.8 total physician visits (95% CI 8.66, 11.07) versus 7.2 (95% CI 6.62, 7.77), and had a 24% (95% CI 19%, 30%) versus 17% (95% CI 14%, 20%) chance of being hospitalized. CONCLUSIONS: Primary care patients who somatize and have high levels of health-related anxiety have considerably higher medical care utilization than nonsomatizers in the year before and after being assessed. This differential persists after adjusting for differences in sociodemographic characteristics and medical morbidity.

Effects of gender and marital status on somatic symptoms of patients attending a mind/body medicine clinic.

To clarify the mechanisms of gender-related mind/body relationships, the authors analyzed the characteristics of 1,132 outpatients (848 women and 284 men) attending a mind/body medicine clinic. At entry in the program, the patients completed the Medical Symptom Checklist, Symptom Checklist-90 revised (SCL-90R), and Stress Perception Scale. Women reported 9 out of 12 symptoms (fatigue, insomnia, headache, back pain, joint or limb pain, palpitations, constipation, nausea, and dizziness) more frequently than the men did. Being a woman was a predictor of the total number of somatic symptoms endorsed. SCL-90R somatization scores were significantly higher in nonmarried women than in married women. Perceived stress ratings of family and health were higher in women than in men, despite the lower degree of perceived stress concerning work. Women, especially nonmarried women, were more likely to report somatic discomfort. Gender appears to be an important factor in relation to the report of somatic symptoms in stress-related conditions.

Somatization and symptom reduction through a behavioral medicine intervention in a mind/body medicine clinic.

The authors assessed data from 1,148 outpatients in a 10-week medical symptom reduction program to determine the effectiveness of a behavioral medicine intervention among somatizing patients. The program included instruction in the relaxation response, cognitive restructuring, nutrition, and exercise. Before and after the intervention, the patients were evaluated on the Symptom Checklist-90 Revised (SCL-90R), the Medical Symptom Checklist, and the Stress Perception Scale. They were divided into high- and low-somatizing groups on the basis of the pretreatment SCL-90R somatization scale. At the end of the program, physical and psychological symptoms on the Medical Symptom Checklist and the SCL-90R were significantly reduced in both groups, with the reductions greater in the high-somatizing group. Improvements in stress perception were about the same in both groups, but the absence of an untreated control group precluded estimates of how much the improvements resulted from the behavioral medicine intervention and how much from natural healing over time.

Depression and education as predicting factors for completion of a behavioral medicine intervention in a mind/body medicine clinic.

The authors compared characteristics of 1,012 outpatients completing a 10-week behavioral medicine intervention with 300 outpatients who dropped out. They administered the Symptom Checklist-90 Revised (SCL-90R) before and after the program. Patients who completed the treatment, compared with dropouts, tended to be more highly educated, married, and gainfully employed. Their pretreatment scores on the SCL-90R were significantly lower than those of the dropouts on somatization, depression, and obsessive-compulsive scales and on the global severity index. Multiple logistic regression analysis indicated that lower depression and higher education marked the group who completed the intervention in contrast to the dropouts. After the intervention, all of the SCL-90R scores were significantly lower among patients who completed the treatment. Pre- to postintervention score changes were not significantly associated with the number of sessions attended. The findings suggest that the intervention had salutary effects in patients with mind/body distress and that its effectiveness was not diminished by a few absences. Depressed or less educated patients might benefit from preparatory interventions or from a modified approach to their treatment.

Palpitations, arrhythmias, and awareness of cardiac activity.

Somatic and visceral symptoms have a surprisingly weak relationship to objective measures of tissue pathology. This is exemplified by the poor correlation found between palpitations and cardiac arrhythmias. Many factors other than extent of disease influence symptomatic distress, and since symptoms are such a crucial feature of illness and of medical practice, much more investigation of these nonbiomedical influences is needed. Although experimental laboratory paradigms facilitate such investigation, there are problems involved in generalizing from laboratory findings to the reporting of the symptoms of disease in daily life. In studying the awareness of cardiac arrhythmias and of resting heartbeat, we have found that the palpitations of patients who somatize more and have more health-related anxiety and more psychiatric distress are significantly less likely to be related to demonstrable cardiac arrhythmias than are the palpitations of other patients. The accurate awareness of arrhythmias, however, is not associated with the accurate awareness of resting heartbeat. Even more surprising, a relatively large proportion of heart transplant recipients are accurately aware of their resting heartbeat. This work poses more questions than it answers. In so doing, it underscores some of the technical difficulties of conducting research in this area and shows how little is known about symptom perception, processing, and reporting.

Hypochondriacal patients' appraisal of health and physical risks.

OBJECTIVE: The authors' goal was to assess the degree to which hypochondriasis is accompanied by a heightened sense of risk of disease and other physical hazards. METHOD: Fifty-six patients meeting DSM-III-R criteria for hypochondriasis were compared with 127 nonhypochondriacal patients from the same primary care setting. Both groups completed a self-report questionnaire assessing the degree to which they felt at risk of developing various medical diseases or being subject to injury from accidents or criminal assault. RESULTS: Both groups of patients exhibited an optimistic bias in that they considered themselves to be less at risk than others of their age and sex. However, the hypochondriacal group had a significantly higher total risk score than did the nonhypochondriacal group. In large part, this intergroup difference was the result of the hypochondriacal patients' perception that they were likely to develop various diseases. The hypochondriacal group did not score significantly higher than the comparison group in estimating their risk of succumbing to accidents and criminal victimization. Perceived risk was significantly associated with the self-reported tendency to amplify benign bodily sensations. CONCLUSIONS: An exaggerated appraisal of risk, jeopardy, and vulnerability to disease may be part of the cognitive distortion seen in hypochondriasis. If this is confirmed, cognitive and behavioral therapies for hypochondriasis may need to include a focus on these patients' understanding and appraisal of risk.

Somatic symptom reporting in women and men.

Women report more intense, more numerous, and more frequent bodily symptoms than men. This difference appears in samples of medical patients and in community samples, whether or not gynecologic and reproductive symptoms are excluded, and whether all bodily symptoms or only those which are medically unexplained are examined. More limited, but suggestive, literature on experimental pain, symptom reporting in childhood, and pain thresholds in animals are compatible with these findings in adults. A number of contributory factors have been implicated, supported by varying degrees of evidence. These include innate differences in somatic and visceral perception; differences in symptom labeling, description, and reporting; the socialization process, which leads to differences in the readiness to acknowledge and disclose discomfort; a sex differential in the incidence of abuse and violence; sex differences in the prevalence of anxiety and depressive disorders; and gender bias in research and in clinical practice. General internists need to keep these factors in mind in obtaining the clinical history, understanding the meaning and significance that symptoms hold for each patient, and providing symptom relief.

Correlation between somatic sensation inventory scores and hyperarousal scale scores.

Somatization mechanisms are poorly understood. The authors tested whether somatization might involve altered central nervous system information processing. They measured somatization using the Somatization Sensation Inventory (SSI) and information processing style using the Hyperarousal Scale, scores of which correlate with electroencephalogram(EEG) measures of cortical electrical responsiveness. SSI scores correlated highly with Hyperarousal scores. On logistic regression, two SSI items and two Hyperarousal items accounted for most of this correlation. These specific hyperarousal items had previously been found to covary with EEG activity and cortical evoked potential amplitudes. The authors concluded that somatization may involve altered CNS processing of somatic stimuli.

Anxiety is a good indicator for somatic symptom reduction through behavioral medicine intervention in a mind/body medicine clinic.

BACKGROUND: This study examined the effect of anxiety on symptom reduction through a behavioral medicine intervention in a Mind/Body Medicine Clinic. METHOD: Participants were 1,312 outpatients attending a 10-week behavioral medicine intervention which included training in the relaxation response, cognitive restructuring, exercise and nutrition. All of the patients had physical symptoms and were referred to the clinic by their physician. The Medical Symptom Checklist (12 major symptoms), Symptom Checklist 90 Revised (SCL-90R), Stress Perception Scale and the Health-Promoting Lifestyle Profile were administered before and after the program. RESULTS: Of the sample, 1,012 patients completed the program, and 911 completed the posttreatment assessment. Self-reported frequency of medical symptoms, degree of discomfort and interference with daily activities were significantly reduced as a result of the program. Anxiety and other psychological distress as measured by the SCL-90R and stress perception scales also showed significant reductions. Furthermore, health-promoting lifestyle functioning significantly improved. High levels of pretreatment anxiety predicted a decrease in the total number of medical symptoms endorsed. CONCLUSIONS: Behavioral medicine interventions are effective in reducing medical symptoms coinciding with improvement in anxiety. High anxiety at program entry may predict better outcome.

Psychiatric symptoms and medical utilization in primary care patients.

In two studies, the authors evaluated the impact of psychiatric disorders on medical care utilization in a primary care setting. In the first study, 526 consecutive patients in a teaching hospital primary care practice completed the 18-item RAND Mental Health Inventory to identify clinically significant depression and/or anxiety and a questionnaire about the use of psychiatric treatment and psychoactive medications. The medical utilization of those patients defined as depressed and/ or anxious was compared with those defined as not depressed and/or anxious. Patients identified as depressed and/or anxious reported significantly increased medical utilization, but this was not confirmed by the hospital's computerized record system. In the second study, the authors analyzed medical care utilization for the years before and after the first outpatient psychiatry appointment of a sample of 91 patients referred from the same primary care practice to the hospital's outpatient psychiatry clinic over a 1-year period. In both studies there was not a statistically significant difference in medical utilization among those patients receiving psychiatric treatment. The findings demonstrate the difficulties in examining cost offset in a primary care population and raise questions about it as a realistic outcome measure of the effect of psychiatric treatment.

Predictors of remission in DSM hypochondriasis.

Although hypochondriasis is generally believed to be a chronic and refractory disorder, relatively little is known about its natural history and course. Based on a cognitive/perceptual model of hypochondriasis, we hypothesized that the disorder would be more chronic in patients who both amplify benign bodily symptoms and tend to attribute them to disease. Thirty-eight patients with DSM hypochondriasis were assessed with a structured, diagnostic interview and self-report questionnaire. A logistic regression model containing sociodemographic characteristics and a 3-way interaction term composed of the tendency to amplify bodily sensations, the tendency to attribute common symptoms to disease, and somatization (all measured at inception) correctly classified the remission status of 81.6% of the patients at follow-up 4 years later. These results suggest that patients who somatize, who are amplifiers of bodily sensation, and those who tend to attribute ambiguous symptoms to disease have more chronic and more refractory hypochondriasis. It is the co-occurrence of these cognitive and perceptual characteristics, rather than their occurrence individually, which predicts the persistence of this disorder.

Heartbeat perception in panic disorder: a reanalysis.

This article describes a reanalysis of seven studies on heart beat perception (HBP) in panic disorder. The pooled sample had 709 participants from eight diagnostic categories. Accurate HBP was uncommon, but more prevalent among panic disorder patients than among healthy controls, depressed patients, patients with palpitations and individuals with infrequent panic attacks. No differences were found between panic disorder patients and patients with other anxiety disorders. Accurate perceivers had higher anxiety sensitivity scores than inaccurate perceivers. The data remain inconclusive as to whether perceived heart rate is correlated with anxiety in inaccurate perceivers. Physical exercise, distraction, variations in instructions and treatment each influenced HBP. However, the influence was different than previously thought. Finally, it is suggested that HBP may be understood in terms of schema-guided information processing.

Perceptual and memory biases for health-related information in hypochondriacal individuals.

Problematic health concerns characteristic of hypochondriasis may be better understood with the aid of cognitive, information processing theories. We investigated whether hypochondriacal individuals show perceptual and explicit memory biases favoring health-related information. A clinical sample of hypochondriacs (n=18) and healthy controls (n=22), and a sample of hypochondriacal (n=22) and nonhypochondriacal (n=67) patients referred for Holter monitoring, completed a computerized test of perceiving difficult-to-read words and then an encoding task followed by recall of those words. Contrary to our prediction, hypochondriacal individuals in the clinical sample did not perceive more health-related words than words not related to health. Hypochondriacal individuals in the Holter-monitoring sample showed an unexpected bias against reporting health-related words. Social class may account for some of the group differences in this sample. Hypochondriacal individuals in both samples showed better memory for health-related than nonhealth words.

Somatic style and symptom reporting in rheumatoid arthritis.

The authors studied the relative contributions of psychological characteristics and rheumatoid arthritis (RA) morbidity to RA symptoms and medication side effects. Thirty-one consecutive patients attending an RA clinic completed self-report questionnaires and diaries assessing RA symptoms and somatic style, a constellation of beliefs, attitudes, and concerns about disease and health. After 3 months, the patients were assessed for RA symptoms and self-reported medication side effects. At inception, RA symptoms were associated with several components of somatic style. At 3-month follow-up, changes in RA symptoms and the incidence of medication side effects were predicted by somatic style variables measured at inception. The symptoms of RA and the side effects of RA pharmacotherapy are prospectively predicted by somatic style as well as by the severity and extent of RA.